The relationship between cognitive and social functioning in older patients with bipolar disorder

Accepted Manuscript

The relationship between cognitive and social functioning in older patients with bipolar disorder.✰ Melis Orhan , Nicole Korten , Max Stek , Hannie Comijs , Sigfried Schouws , Annemiek Dols PII: DOI: Reference:

S0165-0327(18)30076-4 10.1016/j.jad.2018.07.055 JAD 9965

To appear in:

Journal of Affective Disorders

Received date: Revised date: Accepted date:

29 January 2018 1 June 2018 21 July 2018

Please cite this article as: Melis Orhan , Nicole Korten , Max Stek , Hannie Comijs , Sigfried Schouws , Annemiek Dols , The relationship between cognitive and social functioning in older patients with bipolar disorder.✰, Journal of Affective Disorders (2018), doi: 10.1016/j.jad.2018.07.055

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

M

AN US

CR IP T

Highlights  Global cognitive functioning, learning and memory and executive functioning are positively associated with global social functioning  Global social functioning as judged by the clinician is independent of self-reported social functioning  Attention and verbal fluency are not associated with global social functioning

1

ACCEPTED MANUSCRIPT The relationship between cognitive and social functioning in older patients with bipolar disorder.

Melis Orhan1, Nicole Korten1, Max Stek1, 2, Hannie Comijs2, Sigfried Schouws1,2 and

CR IP T

Annemiek Dols1, 2, 3

1 Department of Old Age Psychiatry, GGZinGeest, , Amsterdam, the Netherlands

2 Department of Psychiatry, Amsterdam Public Health research institute, VU University Medical Center, Amsterdam, the Netherlands

AN US

3 Neuroscience Campus VUmc, Amsterdam, the Netherlands

Corresponding author: Melis Orhan, Amstelveenseweg 589, 1081JC, Amsterdam, the

M

Netherlands, [email protected]

ED

Word count: 4.997 (maximum 5.000)

AC

CE

Tables: 2

PT

Figures: 1

2

ACCEPTED MANUSCRIPT Abstract Objectives Patients with bipolar disorder (BD) show specific cognitive impairments, especially in the domains of attention, executive functioning and memory. Social and occupational problems seem to exist in 30-60% of BD patients. This study analysed the relationship

CR IP T

between cognitive and social functioning in older age BD (OABD) patients. Methods

This study included 63 OABD patients (aged >60). Cognitive functioning was measured by an extensive neuropsychological assessment including global cognitive functioning,

AN US

attention, learning and memory, executive functioning and verbal fluency. Social

functioning, was obtained by clinical interview, including global social functioning, meaningful contacts and social participation. Linear regression analyses were

M

conducted between cognitive performance and social functioning and the role of depression severity and disease duration was explored.

ED

Results

PT

Global social functioning, number of meaningful contacts and social participation were not interrelated. Global cognitive functioning, learning and memory and executive

CE

functioning were positively associated with global social functioning. No associations

AC

were found between cognitive functioning and social participation or meaningful contacts. Depression severity and disease duration were no effect modifiers. Limitations

Limitations include the use of a sample with relatively low cognitive and social impairments and the use of a cross-sectional research design. Conclusions

3

ACCEPTED MANUSCRIPT Global social functioning judged by the clinician was found to be independent of social functioning defined by the number of social contacts and social participation as reported by the patient. Global social functioning was related to cognitive functioning. An integrative treatment intervention including cognitive training and addressing social

Keywords: bipolar, impairment, cognitive, social, elderly

CR IP T

functioning may improve daily functioning in OABD patients.

PT

ED

M

commercial, or not-for-profit sectors.

AN US

This research did not receive any specific grant from funding agencies in the public,

AC

CE

,.

4

ACCEPTED MANUSCRIPT Introduction Bipolar disorder (BD) is a chronic mental disorder that is characterized by repeated periods of depression and mania, alternating with complaint-free periods (Clark et al., 2002). Although the number of BD patients seems to decline with age, still 8 – 10% of psychiatric inpatients over age 55-60 are diagnosed with BD (Depp & Jeste, 2004). Due

CR IP T

to our aging society, the number of patients with older age BD (OABD) is growing.

Studies suggest that OABD patients exhibit specific clinical characteristics, differing from adult BD patients (Depp et al., 2005). More insight in OABD functioning will

facilitate tailoring specific treatments for this group, resulting in better treatment

AN US

outcomes and overall functioning.

Attention has recently risen for the cognitive and social aspects of recovery (Judd et al., 2005; Thompson et al., 2005; Robinson & Ferrier, 2006). OABD patients show

M

specific cognitive deficits (Schouws et al., 2007; Schouws et al., 2012; Young et al., 2006), predominantly in the domains of attention, memory, executive functioning and

ED

verbal fluency (Schouws et al., 2009).

PT

Additionally, social and occupational adjustment problems seem to exist in 3060% of BD patients, as shown by a review including several BD patients from different

CE

age groups (MacQueen et al., 2001). Social functioning seems to fluctuate in parallel

AC

with changes in mood symptom severity (Judd et al., 2005), indicating that more depressive symptoms lead to more social dysfunction. Prior studies show that poor social functioning predicts a shorter time to relapse (Gitlin et al., 1995) and more depressive episodes (Gutiérrez-Rojas et al., 2010). Additionally, there might be a gap between clinical and functional outcomes in adult BD patients (age 15-75; Tohen et al., 2000). This indicates that despite a reduction in clinical symptoms, patients might not be functioning on the expected level, with consequences for health-related quality of life

5

ACCEPTED MANUSCRIPT and functioning (Martinez-Aran et al., 2007). Furthermore, age seems to be negatively associated with social functioning in adult BD patients, suggesting that OABD patients experience even more social dysfunction than younger BD patients (Gutiérrez-Rojas et al., 2010). Only a few studies examined the association between cognitive and social

CR IP T

functioning in adult BD patients. In a small (n = 15) study conducted by Zubieta and colleagues (age M = 39, SD = 13; 2001), cognitive impairments in several domains were found. However, only verbal learning and executive functioning were correlated with lower social and occupational functioning. Burdick and colleagues (2010) found that a

AN US

single measure of processing speed was significantly correlated with lower social

functioning over a 12-month period in adult BD patients (n = 33; age M = 40.2, SD = 6.2). In a larger study by Bowie et al. (2010) social competence largely mediated the

M

relationship between cognitive functioning and functional outcomes in adult BD patients (n = 130; age range 18 - 80). In addition, cognitive functioning was directly

ED

related to social activities. Martinez-Aran et al. (2007) pointed out that verbal memory

PT

best predicted psychosocial functioning in BD patients. To our knowledge, the association between cognitive and social functioning in

CE

OABD was only studied once. Van Liempt and colleagues (2016) investigated the

AC

association between cognitive functioning and social functioning in OABD patients (age >60). In this study, OABD patients living in the same catchment area of the mental health institution as their peers with schizophrenia were included from the total cohort of Dutch Older Bipolars (DOBi). A significant association between global cognitive and global social functioning in OABD patients was found. In continuation of these results, the aim of this study is to further investigate the specific relationship between cognitive and social functioning in OABD patients. The current study differs on several aspects

6

ACCEPTED MANUSCRIPT from previous research. To date, most research has been conducted among the younger adult patient population, where our focus will be on OABD patients (>60), considering the different aspects of social functioning including global social functioning, selfreported social participation and network size and various domains of cognitive functioning. Based on previous research we hypothesize that global cognitive

CR IP T

functioning (Van Liempt et al., 2016; Bowie et al., 2010) and learning and memory and executive functioning (Zubieta et al., 2001; Martinez-Aran et al. 2007) are positively associated with social functioning. Since previous research showed stronger

associations between poor cognitive and poor social functioning in more severely

AN US

depressed adult BD patients (Robinson & Ferrier, 2006; Judd et al., 2005), we thereby hypothesize that the positive association between cognitive functioning and social functioning is stronger in OABD patients with more depressive symptoms and a longer

Study sample

ED

Materials and methods

M

disease duration.

PT

For this study data were used from the DOBi study, conducted in 2012 (Dols et al.,

CE

2014). In short, in this study all older patients (aged 60 years and over) in contact with services between January 1, 2012 and December 31, 2012 were identified by a

AC

computerized search in the electronic record-keeping system of the Mental Health Organization (GGZ inGeest, Amsterdam, the Netherlands). Patients were screened for eligibility if they had any registered diagnosis that could indicate bipolar disorder. Inclusion was possible when patients were clinically diagnosed with bipolar I disorder (DSM-IV-TR: 296.00-.06, 296.40- .46, 296.50-.56, 296.60-.66, 296.7), bipolar II disorder (DSM-IV-TR: 296.89) or bipolar disorder not otherwise specified (DSM- IV-TR: 296.80).

7

ACCEPTED MANUSCRIPT Medical records of all potential participants were screened by a psychiatrist for exclusion criteria, including not being able to give written informed consent, not being able to communicate in Dutch or English, mental retardation (IQ < 70), poor cognitive functioning (MMSE <18) or a highly unstable psychiatric condition. Included patients were asked by their psychiatrist or community psychiatric nurse to provide written

CR IP T

consent for participation in the study. 114 patients were eligible for study inclusion. 13 patients were not willing to provide consent or to participate in the study, resulting in 101 patients. 38 patients had no neuropsychological examination or complete social functioning scores available, resulting in a study sample of 63 patients for the current

AN US

study. A flow chart of the study sample is presented in Figure 1. The study was

approved by the Medical Ethics Committee of the VU University Medical Center,

Measurements

ED

Demographic characteristics

M

Amsterdam, the Netherlands.

Demographic data (e.g. age, sex, partner status, level of education) were obtained

PT

through interviews and then checked in patients’ medical records. Education was

CE

divided into low, middle and high. Participants were labelled as low educated if only primary school or low-level high school was completed. Partner status was divided into

AC

having someone they considered as their permanent partner or not. Clinical characteristics Diagnosis of bipolar disorder was confirmed by the Mini-International Neuropsychiatric Interview Plus (MINI; Sheehan et al., 1998), which was performed by experienced clinicians. Duration of the disease (in years since first episode according to DSM-IV criteria) and age of onset were also obtained from the MINI interview. Number of

8

ACCEPTED MANUSCRIPT admissions was obtained by interview. Current mania symptoms were assessed through the Young Mania Rating Scale (YMRS; Young, Biggs, Ziegler & Meyer, 1978). The YMRS is scored on a scale from 0 to 60, with scores ≥ 12 indicating clinically relevant (hypo) mania. Current symptoms of depression were measured by the Center for Epidemiologic Studies Depression Scale (CES-D; Radloff, 1977). The CES-D is a self-

CR IP T

report scale, consisting of 20 items. It measures depressive symptoms during the

previous week, with scores ranging from 0 to 60. Scores ≥ 16 indicate clinically relevant depression.

AN US

Social functioning

Several measurements were conducted to assess social functioning. First, the Social and Occupational Functioning Assessment Scale (SOFAS; APA, 2000) was conducted to assess the level of global social functioning in the previous week, as estimated by

M

patients’ treating psychiatrist. The achieved score is a global rating of current social

ED

functioning ranging from 1 to 100, with lower scores indicating lower social functioning, and scores ≥ 90 suggesting no social impairments. Benchmarks are based

PT

on the quality of several areas concerning social functioning, such as containing

CE

personal hygiene, the quality of patients’ contacts and occupational functioning. Second, the Social Participation Scale (SPS; Depla, De Graaf et al., 2003) was used to measure

AC

self-report of involvement in 10 different social activities (e.g. doing groceries, doing sports or attending a church service). Possible answers are never, rarely or regularly. Higher scores indicate more regular participation in social activities. Third, patients’ social network was assessed through the self-reported number of persons outside their household with whom they have regular and meaningful contact. Cognitive functioning

9

ACCEPTED MANUSCRIPT Global cognitive functioning was assessed by the Mini Mental State Examination (MMSE; Folstein et al., 1975). In addition, subjects completed an extensive neuropsychological assessment, which involved tests on multiple cognitive domains as used in Schouws and colleagues (2010), including: Attention: Digit Span subtest of the Wechsler Adult Intelligence Scale (WAIS-III;

CR IP T

-

Wechsler, 1981), Trail Making Test part A (Reitan, 1958) -

Learning and memory: The 10 Words Test (learning – retention – recognition), a modified version of the Auditory Verbal Learning Test (Rey, 1964)

Executive functioning: Trail Making Test part B (Reitan, 1958), Modified version

AN US

-

of the Stroop Color Word Test (Golden, 1978), Mazes (1 to 4) subtest of the Wechsler Intelligence Scale for Children (WISC) (Wechsler, 1976), and the Rule

(Wilson et al., 1996)

Verbal fluency: Control Oral Word Association Test (COWAT; Benton and

ED

-

M

Shift Cards subtest of the Behavioral Assessment of the Dysexecutive Syndrome

Hamsher, 1976), Animal and Occupation Naming subtest of the Groningen

PT

Intelligence Test (GIT; Luteijn & Van der Ploeg, 1983)

CE

Higher scores on the domains of attention and executive functioning indicate worse cognitive functioning and lower scores on the domains of learning and memory and

AC

verbal fluency indicate worse cognitive functioning.

Statistical analysis Data were analysed using the Statistical Package of the Social Sciences (version 24.0, SPSS Inc., Chicago, IL, USA). First, descriptive analyses were performed for demographic and clinical characteristics, social functioning scores and cognitive functioning scores.

10

ACCEPTED MANUSCRIPT Differences between the total cohort and the current study sample were calculated through t-tests for continuous variables or chi-square tests for categorical variables. A Mann-Whitney U test was used when the assumption of normality was not reached. For neuropsychological functioning, raw test scores were transformed into z-scores. The mean of these z-scores was used to compose functioning scores per cognitive domain.

CR IP T

MMSE, SOFAS, SPS and CES-D scores were log transformed to obtain a near-normal distribution. To observe if the different social functioning measures were interrelated, Pearson’s r has been conducted between the different aspects of social functioning. Separate regression analyses were conducted with the cognitive domains as

AN US

independent variables and aspects of social functioning as dependent variables. Next, age, level of education and depressive symptoms will be entered as covariates. The role of mood symptom severity (CES-D score) and disease duration was explored

M

separately through the addition of an interaction-term with global cognitive functioning

ED

in the regression analysis that studied the association between global cognitive and global social functioning. When finding significant interaction effects (p < 0.05),

PT

stratified analyses will be conducted in the different groups. Results with a p < 0.05 will

Results

CE

be regarded as statistically significant.

AC

Demographic and clinical characteristics The demographic and clinical characteristics of the patients with no neuropsychological data available (N = 38) and the study sample (N = 63) are summarized in Table 1. The median of the age of the participants in the study sample was 67 (IQR = 15) and gender was equally distributed. The majority of patients had children (73%). The median of the duration of the bipolar disorder was 38 years (IQR = 20) with an median of age of onset

11

ACCEPTED MANUSCRIPT of 30 years (IQR = 24). Participants were not depressed or (hypo) manic at the time of testing as indicated by low YMRS scores (median = 3, IQR = 4) and low CES-D scores (median = 7, IQR = 15). To study possible selection bias we examined differences in demographic and clinical characteristics between the complete sample and the study

partner, and had less psychiatric admissions (Table 1).

Social functioning

CR IP T

sample. Patients that did not participate in the study sample were less likely to have a

Social functioning scores are reported in Table 1. The median of the SOFAS of the study

AN US

sample was 65 (IQR = 15), indicating that the study sample experienced moderate social impairments. The median of the Social Participation Scale was 12 (IQR = 4), suggesting that participants are involved at least on a regular basis in some of the 10 inquired

M

activities (maximum score is 20). 30.2% of participants reported that they regularly have meaningful contact with 6 – 10 persons outside their household. No high

ED

correlations (all r < .30) were found between SOFAS scores, social participation and

PT

meaningful contacts, indicating that the measured aspects of social functioning are not

CE

highly interrelated.

AC

Cognitive functioning

Table 1 shows the scores on each cognitive domain. Most participants showed no global cognitive dysfunction as indicated by high MMSE scores (median = 28, IQR = 2).

Association between cognitive and social functioning The results from linear regression analyses between global cognitive functioning and global social functioning (SOFAS) appeared significant (β = .37, p = .003) and remained

12

ACCEPTED MANUSCRIPT significant when controlling for the confounding variables age, level of education and depressive symptoms (β = .31, p = .02)(Table 2). Separate linear regression analyses were conducted to determine if the individual cognitive domains were associated with the several aspects of social functioning corrected for age, level of education and depressive symptoms (Table 2). The association between attention and global social

CR IP T

functioning appeared significant (β = -.30, p = .019), but did not remain significant when adjusting for age, level of education and depressive symptoms (β = -.257, p = .06).

Learning and memory showed a significant association with SOFAS scores as well (β = .32, p = .011) and remained significant when entering the confounding variables into the

AN US

regression model. A significant association was also found for executive functioning (β = -.47, p <.01), which remained significant when entering the confounding variables into the regression model. Linear regression analysis between verbal fluency and global

M

social functioning appeared significant (β = .26, p = .04), but did not remain significant when entering confounding variables into the regression model. When entering the

ED

confounding variables in a stepwise manner, attention and verbal fluency appear non-

PT

significant after entering CES-D score into the model. The association between the cognitive domains, and respectively social participation

AC

CE

and the number of meaningful contacts were not statistically significant (Table 2).

Mood symptom severity and disease duration in relation to cognitive and social functioning

To explore the role of mood symptom severity and disease duration in the association between global cognitive functioning and the aspects of social functioning, interaction terms were entered in the regression models. None of the interaction-terms were statistically significant (all p>0.05).

13

ACCEPTED MANUSCRIPT

Discussion The aim of this study was to investigate the relationship between cognitive functioning and quantitative and qualitative measures of social functioning in OABD patients. We found a significant positive association between global cognitive and global social

CR IP T

functioning as judged by the clinician. By looking closely into the different aspects of cognitive and social functioning, the domains learning and memory and executive functioning were found to be positively associated with global social functioning, whereas attention and verbal fluency were not. Cognitive functioning was not

AN US

associated with social participation and the number of meaningful contacts as reported by the patients. Additionally, it was found that the different aspects of social functioning were not interrelated.

M

No associations were found between social participation and meaningful contacts and the several aspects of cognitive functioning. In Bowie et al. (2010), it was

ED

found that social activities were directly associated with cognitive functioning. This

PT

discrepancy in results could be explained by the fact that our measure of social participation was self-reported, where social activities in Bowie et al. (2010) was

CE

observer-rated. We found significant results between the SOFAS and cognitive

AC

functioning, where we did not find significant associations between social participation and meaningful contacts and cognitive functioning. As mentioned before, the SOFAS score is an estimate made by the treating psychiatrist, while social participation and meaningful contacts are self-reported. This discrepancy is supported by the finding that our measured aspects of social functioning appeared not to be highly interrelated, what indicates that we measured different aspects of social functioning. The SOFAS indicates if there are any problems in social functioning and focuses on the quality of social

14

ACCEPTED MANUSCRIPT functioning in several areas, for example; maintaining personal hygiene, functioning in work and maintaining family and other interpersonal relations. Therefore, it is particularly an indication of the quality of social functioning. On the other hand, the social participation scale and the number of meaningful contacts are an indication of the quantity of social functioning. The social participation scale and the number of

CR IP T

meaningful contacts do not indicate directly if there are any problems in patients’ social functioning. For example, in the context of social participation; social services are highly available for the older adult population in the Netherlands. So despite experiencing

cognitive impairments, it is still possible to participate in social activities. These findings

AN US

might suggest that observer-rated measurements might be a better estimate of

problems in social functioning that is not in line with self-reported aspects of social functioning. An additional option to improve the estimation of the quality of social

M

functioning is to include qualitative self-report measurements, since social cognition is relatively preserved in adult bipolar patients (Samamé, Martino & Strejilevich, 2014)

ED

Conforming our hypothesis and in line with findings in younger adult BD

PT

patients, our findings suggest that better global cognitive functioning is associated with better global social functioning in OABD. This is in line with our previous study (Van

CE

Liempt et al., 2016). In this study, a subset of OABD from the DOBi cohort was compared

AC

with their peers with schizophrenia living in the same catchment area using the same instruments to indicate global cognitive and global social functioning. Contrary with our hypothesis, no significant interaction effects were found for

symptom severity and disease duration. An explanation for this finding could be that YMRS and CES-D scores were relatively low in our study sample, indicating that the study sample was a relatively healthy group of patients with little or no mood symptoms at the time of testing. As mentioned before in Judd et al. (2005), it seems that

15

ACCEPTED MANUSCRIPT psychosocial functioning fluctuates along with mood symptoms. This indicates that, since our study sample showed little or no mood symptoms at the time of testing, these psychosocial impairments might have been limited. With respect to the role of disease duration, previous results were mixed (Robinson et al., 2006). Our results suggest that disease duration does not interact in the association between cognitive and social

CR IP T

functioning.

Besides finding an association between better global cognitive functioning and better global social functioning, we found that better learning and memory and better executive functioning were associated with better global social functioning. To our

AN US

knowledge no other study has been conducted before focusing on the association between different aspects of cognitive and social functioning in the OABD patient

population. However, our results are in line with prior publications in adult BD patients,

M

where different studies found mixed results regarding the domains that have an association with cognitive functioning. Martinez-Alan and colleagues (2007) compared

ED

a group of adult BD patients with high psychosocial functioning with a group of adult BD

PT

patients with low psychosocial functioning. It was found that verbal memory seemed to be a good predictor of social functioning in adult BD patients. Besides finding an

CE

association between verbal memory and social functioning, Zubieta and colleagues

AC

(2001) compared a group of adult BD patients with healthy controls and also found an association between executive functioning and social functioning in adult BD patients. Both studies did not take into account other cognitive domains, since scores on these domains did not differ between adult BD patients and the control group. However, in a meta-analysis conducted in adult BD patients (Depp et al., 2012), it was observed that all cognitive domains showed associations with global social functioning. Our study has several strong points. In contrast to earlier studies, where

16

ACCEPTED MANUSCRIPT functioning scores often consisted of limited number of measurements, we aimed to sketch a more complete view of both aspects of functioning by using more comprehensive measurements. This enhances the generalizability of our study results to real-world situations. To our knowledge no other study was conducted before focusing on the relationship between cognitive functioning and social functioning in the

CR IP T

OABD patient population. Besides these strong points, there are some limitations that need to be acknowledged. First, our study we included participants that experienced little or no mood symptoms and little impairments in cognitive (MMSE <18) or social functioning, but hardly any potential participant was excluded for this criterion.

AN US

However, as mentioned in the results section, a selection bias was present. These issues limit the generalizability of our results to most impaired patients. Thereby, a relatively small sample size and a cross-sectional study design were used, therefore we cannot

M

make statements about the predictive value of the variables and studying potential moderators and mediators was limited.

ED

Our results emphasize that better cognitive functioning is associated with better

PT

social functioning in OABD patients. These findings warrant specific clinical implications. When during the diagnostic process cognitive deficits are observed, it

CE

needs to be taken into account that these deficits can cause impairments in social

AC

functioning. Vice versa, when social impairments are observed, one should be alert on additional cognitive deficits. The finding that the different aspects of social functioning are not interrelated stresses the need to include different aspects of social functioning in composing a reliable social functioning estimate. In conclusion, our findings suggest that better functioning in learning and memory and executive functioning is associated with better global social functioning in OABD patients. For improving daily functioning in OABD patients, it seems of great

17

ACCEPTED MANUSCRIPT importance to develop an integrative treatment program in which the quality of social and cognitive functioning is being addressed and improved. Suggestion for further research is to look into the association between cognitive and social functioning in a longitudinal study design to draw conclusions about the direction of the association between cognitive and social functioning in OABD patients and to study potential

CR IP T

moderators and mediators.

Literature

APA. (2000). Diagnostic and statistical manual of mental disorders. Washington, DC:

AN US

American Psychiatric Press.

Benton, A.L., & Hamsher, K. (1976). Multilingual aphasia examination. Iowa City, IA: University of Iowa.

M

Bowie, C.R., Depp, C., McGrath, J.A., Wolyniec, P., Mausbach, B.T., Thornquist, M.H., . . . Pulver, A.E. (2010). Prediction of real-world functional disability in chronic mental

ED

disorders: A comparison of schizophrenia and bipolar disorder. American Journal of

PT

Psychiatry, 167(9), 1116–1124.

Burdick, K.E., Goldberg, J.F., & Harrow, M. (2010). Neurocognitive dysfunction and

CE

psychosocial outcome in patients with bipolar I disorder at 15-year follow-up. Acta

AC

Psychiatric Scandinavia, 122(6), 499– 506. Clark, L., Iversen, S.D., & Goodwin, G.M. (2002). Sustained attention deficit in bipolar disorder. The British Journal of Psychiatry, 180(4), 313–319. Depla, M.F., De Graaf, R., Van Bussbach, J.T., & Heeren, T.J. (2003). Community integration of elderly mentally ill persons in psychiatric hospitals and two types of residences. Psychiatric Services, 54(5), 730–735.

18

ACCEPTED MANUSCRIPT Depp, C.A., & Jeste, D.V. (2004). Bipolar disorder in older adults: A critical review. Bipolar Disorders, 6(5), 343–367. Depp, C.A., Lindamer, L.A., Folsom, D.P., Gilmer, T., Hough, R.L., Garcia, P., & Jeste, D.V. (2005). Differences in clinical features and mental health service in bipolar disorder across the lifespan. American Journal of Geriatric Psychiatry, 13(4), 290–298.

CR IP T

Depp, C.A., Mausbach, B.T., Harmell, A.L., Savla, G.N., Bowie, C.R., Harvey, P.D., &

Patterson, T.L. (2012). Meta-analysis of the association between cognitive abilities and everyday functioning in bipolar disorder. Bipolar Disorders, 14(3), 217–2226.

Dols, A., Rhebergen, D., Beekman, A., Kupka, R., Sajatovic, M., & Stek, M.L. (2014).

AN US

Psychiatric and medical comorbidities: Results from a bipolar elderly cohort study. American Journal of Geriatric Psychiatry, 22(11), 1066–1074.

Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). “Mini-mental state”: A practical

research, 12(3), 189–198.

M

method for grading the cognitive state of patients for the clinician. Journal of psychiatric

ED

Gitlin, M.J., Swendsen, J., Heller, T.L., & Hammen, C. (1995). Relapse and impairment in

PT

bipolar disorder. American Journal of Psychiatry, 152(11), 1635–1640. Golden, C.J. (1978). Stroop color word test. Chicago, Illinois: Stroeting.

CE

Gutiérrez-Rojas, L., Jurado, D., &, Gurpegui, M. (2010). Factors associated with work,

AC

social life and family life disability in bipolar disorder patients. Psychiatry Research, 186(2-3), 254–260. Judd, L.L., Akiksal, H.S., Schettler, P.J., Endicott, J., Leon, A.C., Solomon, D.A., . . . Keller, M.B. (2005). Psychosocial disability in the course of bipolar I and II disorder. Archives of General Psychiatry, 62(12), 1322–1330. Luteijn, F., & Van der Ploeg, F.A.E. (1983). Handleiding Groninger intelligentietest (GIT) (Manual Groningen intelligence test). Lisse, The Netherlands: Swets and Zeitlinger.

19

ACCEPTED MANUSCRIPT MacQueen, G.M., Young, L.T., & Joffe, R.T. (2001). A review of psychosocial outcome in patients with bipolar disorder. Acta Psychiatrica Scandinavia, 103(3), 163–170. Martinez-Aran, A., Vieta, E., Torrent, C., Sanchez-Moreno, J., Goikolea, J.M., Salamero, M., . . . R.,Ayuso-Mateos, J.L. (2007). Functional outcome in bipolar disorder: The role of clinical and cognitive factors. Bipolar Disorders, 9(1-2), 103–113.

CR IP T

Radloff, C.S. (1977). The CES-D scale: A self-report depression scale for research in the general population. Applied Psychological Measurement, 1(3), 385–401.

Reitan, R.M. (1958). Validity of the trailmaking test as an indication of organic brain damage. Perceptual and Motor Skills 8(3), 271–276.

AN US

Rey, A. (1964). L'examen clinique en psychologie. Paris: Presses Universitaires de France. Robinson, L.J., & Ferrier, I.N. (2006). Evolution of cognitive impairment in bipolar disorder: A systematic review of cross-sectional evidence. Bipolar Disorders, 8(2), 103–

M

116.

Samamé, C., Martino, D.J., & Strejilevich, S.A. (2012). Social cognition in euthymic bipolar

ED

disorder: systematic review and meta-analytic approach. Acta Psychiatrica

PT

Scandinavica, 125(4), 266-280.

Sanchez-Moreno, J., Martinez-Aran, A., Tabarés-Seisdedos, R., Torrent, C., Vieta, E., &

CE

Ayuso-Mateos, J.L. (2009). Functioning and disability in bipolar disorder: An extensive

AC

review. Psychotherapy and Psychosomatics, 78(5), 285–297. Schouws, S.N.T.M., Stek, M.L., Comijs, H.C., & Beekman, A.T. (2010). Risk factors for cognitive impairment in elderly bipolar patients. Journal of Affective Disorders, 125(1-3), 330–335. Schouws, S.N.T.M., H.C., Comijs, Stek, M.L., Dekker, J., Oostervink, F., Naarding, P., . . . Beekman, A.T. (2009). Cognitive impairment in early and late bipolar disorder. American Journal of Geriatric Psychiatry, 17(6), 508–515.

20

ACCEPTED MANUSCRIPT Schouws, S.N.T.M., Zoeteman, J.B., Comijs, H.C., Stek, M.L. & Beekman, A.T.F. (2007). Cognitive functioning in elderly patients with early onset bipolar disorder. International Journal of Geriatric Psychiatry, 22(6), 856–861. Schouws, S.N.T.M., Comijs, H.C., Dols, A., Beekman, A.T.F., Stek, M.L. (2016). Five-year

Disorders, 18(2), 148–154.

CR IP T

follow-up of cognitive impairment in older adults with bipolar disorder. Bipolar

Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E., . . . Dunbar, G.C. (1998). The mini-international neuropsychiatric interview (M.I.N.I.): The

development and validation of a structured diagnostic psychiatric interview for DSM-IV

AN US

and ICD-10. Journal of Clinical Psychiatry, 59(20), 22–33.

Thompson, J.M., Gallagher, P., Hughes, J.H., Watson, S. Gray, J.M., Ferrier, N., & Young, A.H. (2005). Neurocognitive impairment in euthymic patients with bipolar affective

M

disorder. The British Journal of Psychiatry, 186(1), 32–40.

Tohen, M., Hennen, J., Zarate, C.M., Baldessarini, R.J., Strakowski, S.M., Stoll, A.L., . . .

ED

Cohen, B.M. (2000). Two-year syndromal and functional recovery in 219 cases of first-

PT

episode major affective disorder with psychotic features. American Journal of Psychiatry, 157(2), 220 – 228.

CE

Van Liempt, S., Dols, A., Schouws, S., Stek, M.L., & Meesters, P.D. (2016). Comparison of

AC

social functioning in community living older individuals with schizophrenia and bipolar disorder: A catchment area-based study. International Journal of Geriatric Psychiatry, 32(5), 532–538. Wechsler, D. (1976). Wechsler intelligence scale for children — revised UK edition. Windsor: NFER- Nelson. Wechsler, D. (1981). WAIS-R manual, Wechsler adult intelligence scale - revised. Cleveland, OH: Psychological Corporation.

21

ACCEPTED MANUSCRIPT Wilson, B.A., Alderman, N., Burgess, P.W., Emslie, H., Evan, J.J. (1996). Behavioural assessment of the dysexecutive syndrome. Bury St. Edmunds, England: Thames Valley Test Company. Young, R.C., Biggs, J.T., Ziegler, V.E., Meyer, D. (1978). A rating scale for mania: Reliability, validity and sensitivity. British Journal of Psychiatry, 133(5), 429–435.

CR IP T

Young, R.C. Murphy, C.F., Heo, M., Schulberg, H.C. &, Alexopoulos, G.S. (2006). Cognitive impairment in bipolar disorder in old age: Literature review and findings in manic patients. Journal of Affective Disorders, 92(1), 125–131.

Zubieta, J. Huguelet, P., Lajiness O’Neil, R. & Giordani, B.J. (2001). Cognitive function in

AC

CE

PT

ED

M

AN US

euthymic bipolar I disorder. Psychiatry Research, 102(1), 9–20.

22

ACCEPTED MANUSCRIPT Patients screened for eligibility n = 139

Not eligible for inclusion n = 25 - language barrier n = 1 - mental retardation n = 4 - dementia n = 8 - very unstable n = 1 - died n = 1 - different diagnosis n = 10 (mood disorder NOS n = 3, personality disorder n = 2, schizoaffective disorder n = 3, cyclothym disorder n = 1, recurrent depression n = 1)

Eligible for study inclusion n = 114

CR IP T

Not willing to provide consent or to participate n =13 Patients for clinical interviews n = 78 Patients for review of records n = 23, resulting in the total study sample n = 101

Patients with complete social functioning scores and neuropsychological examination n = 63

AC

CE

PT

ED

M

Figure 1. Flow chart of the study sample.

AN US

No neuropsychological examination or complete social functioning scores available n = 38

23

ACCEPTED MANUSCRIPT

Table 1 Descriptive variables (demographic, clinical, social and cognitive characteristics) of the total cohort and the study sample

Statistics: X2 / t (df) p

Not included

Study sample

N = 38

N = 63

67 (15), 61 – 98

66 (10), 61 – 85

MW .16

60.5 (23)

49.2 (31)

1.22 (1) .27

Age, median (IQR), range Female, % (n) Partner status, yes, % (n)

25 (4)

63.5 (40)

7.66 (1) <.01

73 (46)

0.68 (1) .41

27 (17)

.001 (1) .98

19 (12)

6.81 (8) .56

6.4 (4)

7.08 (4) .13

33 (19), 17 – 55

30 (24), 8 – 72

MW .76

35 (20), 7 – 81

38 (20), 2 – 59

MW .66

0 (0), 0 – 0

1 (3), 0 – 17

MW <.01

Children, yes, % (n)

62.5 (10)

Pet, yes, % (n)

26.7 (4)

Level of education, low, % (n)

37.5 (6)

Place of residence, residential care, % (n)

25 (4)

Clinical characteristics

AN US

Age of onset, median (IQR), range Duration of disease, median (IQR), range Psychiatric admissions, median (IQR), range YMRS, median (IQR), range CES-D, median (IQR), range Social functioning

ED

2-5

> 10 Cognitive functioning

PT

6 – 10

MW .16 MW. 63

9 (6), 1 – 16

12 (4), 5 – 17

MW .35

65 (15) 35 – 85

MW .18 7.60 (5) .18

8.3 (3)

4.8 (3)

72.2 (26)

41.3 (26)

30.2 (19)

30.2 (19)

23.8 (15)

28.3 (15)

29 (2), 24 – 30

28 (2), 24 – 30

CE

MMSE, median (IQR), range Attention

3 (4), 0 – 27

7 (15), 0 – 45

60 (16), 45 – 85

Meaningful contacts, % (n) 0-1

4 (9), 0 – 25

11 (13), 0 – 35

M

Social participation, median (IQR), range SOFAS score, median (IQR), range

CR IP T

Demographics

Digits forward, M (SD)

5.4 (1.2)

Digits backward, M (SD)

3.9 (1.2) 60.6 (38.8)

AC

Trail Making Test part A (sec), M (SD) Learning and memory

10 Words test Learning (1-5), M (SD)

30.6 (8.3)

10 Words test Recall, M (SD)

4.7 (2.5)

10 Words test Recognition, M (SD)

18.0 (2.6)

Executive functioning Trail Making Test part B, M (SD)

167.6 (130.7)

Stroop test III* (line 1 – 4), M (SD)

59.1 (50.4)

WISC Mazes (sec), M (SD)

147.5 (128.8)

BADS Rule Shift Cards (score), M (SD)

2.9 (1.1)

Verbal fluency

24

MW .41

ACCEPTED MANUSCRIPT 27.6 (13.2)

Animal Naming, M (SD)

20.6 (6.8)

Occupational Naming, M (SD)

15.2 (5.9)

AC

CE

PT

ED

M

AN US

CR IP T

D – A – T Letter fluency, M (SD)

25

ACCEPTED MANUSCRIPT Table 2 The association between cognitive functioning and social functioning in older age bipolar patients with age, level of education and depressive symptoms as confounding variables Social participation

SOFAS score (log

(log transformed)

transformed)

Meaningful contacts

p

β

p

β

p

.15

.26

.31

.02

-.07

.60

Attention

-.17

.22

-.25

Learning and memory

.24

.11

.33

Executive functioning

.05

.75

-.53

Verbal fluency

.03

.83

.19

MMSE (log

.06

-.09

.50

.02

-.10

.53

<.01

-.07

.66

.18

.04

.77

AN US

transformed)

CR IP T

β

AC

CE

PT

ED

M

Note. Linear regression analyses were conducted with age, level of education and depressive symptoms as confounding variables. Independent variables and confounding variables were entered simultaneously into the regression model. OABD, older age bipolar disorder; SOFAS, Social and Occupational Functioning Scale; MMSE, Mini Mental State Examination; β, standardized regression coefficients.

26